Publications by authors named "Yu Li"

4,572 Publications

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A novel nomogram with preferable capability in predicting the overall survival of patients after radical esophageal cancer resection based on accessible clinical indicators: A comparison with AJCC staging.

Cancer Med 2021 Jun 15. Epub 2021 Jun 15.

Department of Thoracic Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

Background: Esophageal cancer (EC) is a malignant tumor with high mortality. Nomogram is an important tool used in clinical prognostic assessment. We aimed to establish a novel nomogram to predict the overall survival (OS) of EC patients after radical esophagectomy.

Methods: Data pertaining to the survival, demography, and clinicopathology of 311 EC patients who underwent radical esophagectomy were retrospectively investigated. The nomogram was established based on Cox hazard regression analysis. The calibration curves and Harrell's concordance index (C-index) were used to verify the predictive accuracy and ROC curves were used to assess the efficacy of the nomogram. Kaplan-Meier curves showed the prognostic value of the related risk classification system. Pearson correlation test was performed to determine the correlation between the risk classification system and TNM staging.

Results: The median OS and 5-year survival rates in the primary and validation cohorts were 44 months and 29.8%, and 52 months and 27.1%, respectively. We used six independent prognostic factors-age, Sex, AGR, PRL, N stage, and PNI-in the nomogram. The C-index of nomogram was 0.75 and 0.70 in the primary and validation cohorts, respectively. Calibration curves indicated high consistency between actual and predicted OS. ROC curves showed that nomogram has a better efficacy compared with TNM staging in both cohorts. Patients were divided into three risk groups according to the total nomogram score, the median OS in each group was significantly different in both cohorts. Furthermore, the risk classification system was strongly correlated with the T and N staging system and exhibited a better OS prediction capability.

Conclusions: We established a novel and practical nomogram with a subordinate risk classification system to predict the OS of patients after radical esophagectomy. Compared with AJCC staging, this nomogram had preferable clinical capability in terms of individual prognosis assessment.
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http://dx.doi.org/10.1002/cam4.3878DOI Listing
June 2021

C/EBP homologous protein deficiency enhances hematopoietic stem cell function via reducing ATF3/ROS-induced cell apoptosis.

Aging Cell 2021 Jun 15:e13382. Epub 2021 Jun 15.

Key Laboratory of Regenerative Medicine of Ministry of Education, Institute of Aging and Regenerative Medicine, Jinan University, Guangzhou, China.

Hematopoietic stem cells (HSCs) reside in a quiescent niche to reserve their capacity of self-renewal. Upon hematopoietic injuries, HSCs enter the cell cycle and encounter protein homeostasis problems caused by accumulation of misfolded proteins. However, the mechanism by which protein homeostasis influences HSC function and maintenance remains poorly understood. Here, we show that C/EBP homologous protein (CHOP), demonstrated previously to induces cell death upon unfolded protein response (UPR), plays an important role in HSCs regeneration. CHOP mice showed normal hematopoietic stem and progenitor cell frequencies in steady state. However, when treated with 5-FU, CHOP deficiency resulted in higher survival rates, associated with an increased number of HSCs and reduced level of apoptosis. In serial competitive transplantation experiments, CHOP HSCs showed a dramatic enhancement of repopulation ability and a reduction of protein aggresomes. Mechanistically, CHOP deletion causes reduced ATF3 expression and further leads to decreased protein aggregation and ROS. In addition, CHOP HSCs exhibited an increased resistance to IR-induced DNA damage and improved HSCs homeostasis and function in telomere dysfunctional (G3Terc ) mice. In summary, these findings disclose a new role of CHOP in the regulation of the HSCs function and homeostasis through reducing ATF3 and ROS signaling.
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http://dx.doi.org/10.1111/acel.13382DOI Listing
June 2021

mTORC2 regulates ribonucleotide reductase to promote DNA replication and gemcitabine resistance in non-small cell lung cancer.

Neoplasia 2021 Jun 11;23(7):643-652. Epub 2021 Jun 11.

Department of Medical Biochemistry and Molecular Biology, School of Medicine, MOE Key Laboratory of Tumor Molecular Biology, Jinan University, Guangzhou, China. Electronic address:

Ribonucleotide reductase (RNR) is the key enzyme that catalyzes the production of deoxyribonucleotides (dNTPs) for DNA replication and it is also essential for cancer cell proliferation. As the RNR inhibitor, Gemcitabine is widely used in cancer therapies, however, resistance limits its therapeutic efficacy and curative potential. Here, we identified that mTORC2 is a main driver of gemcitabine resistance in non-small cell lung cancers (NSCLC). Pharmacological or genetic inhibition of mTORC2 greatly enhanced gemcitabine induced cytotoxicity and DNA damage. Mechanistically, mTORC2 directly interacted and phosphorylated RNR large subunit RRM1 at Ser 631. Ser631 phosphorylation of RRM1 enhanced its interaction with small subunit RRM2 to maintain sufficient RNR enzymatic activity for efficient DNA replication. Targeting mTORC2 retarded DNA replication fork progression and improved therapeutic efficacy of gemcitabine in NSCLC xenograft model in vivo. Thus, these results identified a mechanism through mTORC2 regulating RNR activity and DNA replication, conferring gemcitabine resistance to cancer cells.
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http://dx.doi.org/10.1016/j.neo.2021.05.007DOI Listing
June 2021

Immunological Identification and Characterization of the Capsid Scaffold Protein Encoded by UL26.5 of Herpes Simplex Virus Type 2.

Front Cell Infect Microbiol 2021 26;11:649722. Epub 2021 May 26.

Institute of Medical Biology, Chinese Academy of Medicine Sciences & Peking Union Medical College, Yunnan Key Laboratory of Vaccine Research and Development for Severe Infectious Diseases, Kunming, China.

Herpes simplex virus type 2 (HSV2), a pathogen that causes genital herpes lesions, interferes with the host immune system various known and unknown mechanisms. This virus has been used to study viral antigenic composition. Convalescent serum from HSV2-infected patients was used to identify viral antigens 2-D protein electrophoresis and immunoblotting. The serum predominantly recognized several capsid scaffold proteins encoded by gene UL26.5, mainly ICP35. This protein has been primarily reported to function temporarily in viral assembly but is not expressed in mature virus particles. Further immunological studies suggested that this protein elicits specific antibody and cytotoxic T lymphocyte (CTL) responses in mice, but these responses do not result in a clinical protective effect in response to HSV2 challenge. The data suggested that immunodominance of ICP35 might be used to design an integrated antigen with other viral glycoproteins.
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http://dx.doi.org/10.3389/fcimb.2021.649722DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8187855PMC
May 2021

Sociodemographic and clinical correlates of gabapentin receipt with and without opioids among a national cohort of patients with HIV.

AIDS Care 2021 Jun 11:1-11. Epub 2021 Jun 11.

Yale School of Medicine, New Haven, CT, USA.

Gabapentin is commonly prescribed for chronic pain, including to patients with HIV (PWH). There is growing concern regarding gabapentin's potential for harm, particularly in combination with opioids. Among PWH, we examined factors associated with higher doses of gabapentin receipt and determined if receipt varied by opioid use. We examined data from the Veterans Aging Cohort Study, a national prospective cohort including PWH, from 2002 through 2017. Covariates included prescribed opioid dose, self-reported past year opioid use, and other sociodemographic and clinical variables. We used multinomial logistic regression to determine independent predictors of gabapentin receipt. Among 3,702 PWH, 902 (24%) received any gabapentin during the study period at a mean daily dose of 1,469 mg. In the multinomial model, high-dose gabapentin receipt was associated with high-dose benzodiazepine receipt (adjusted odds ratio [aOR], 95% confidence interval [CI]= 1.53, [1.03-2.27]), pain interference (1.65 [1.39-1.95]), and hand or foot pain (1.81, [1.45-2.26]). High-dose gabapentin receipt was associated with prescribed high-dose opioids receipt (2.66 [1.95-3.62]) but not self-reported opioid use (1.03 [0.89-1.21]). PWH prescribed gabapentin at higher doses are more likely to receive high-dose opioids and high-dose benzodiazepines, raising safety concerns.
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http://dx.doi.org/10.1080/09540121.2021.1939851DOI Listing
June 2021

Hybrid AI-assistive diagnostic model permits rapid TBS classification of cervical liquid-based thin-layer cell smears.

Nat Commun 2021 06 10;12(1):3541. Epub 2021 Jun 10.

Department of Pathology, Guangdong Provincial Women's and Children's Dispensary, Shenzhen, Guangdong Province, PR China.

Technical advancements significantly improve earlier diagnosis of cervical cancer, but accurate diagnosis is still difficult due to various factors. We develop an artificial intelligence assistive diagnostic solution, AIATBS, to improve cervical liquid-based thin-layer cell smear diagnosis according to clinical TBS criteria. We train AIATBS with >81,000 retrospective samples. It integrates YOLOv3 for target detection, Xception and Patch-based models to boost target classification, and U-net for nucleus segmentation. We integrate XGBoost and a logical decision tree with these models to optimize the parameters given by the learning process, and we develop a complete cervical liquid-based cytology smear TBS diagnostic system which also includes a quality control solution. We validate the optimized system with >34,000 multicenter prospective samples and achieve better sensitivity compared to senior cytologists, yet retain high specificity while achieving a speed of <180s/slide. Our system is adaptive to sample preparation using different standards, staining protocols and scanners.
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http://dx.doi.org/10.1038/s41467-021-23913-3DOI Listing
June 2021

Mechanistic insights into the R-loop formation and cleavage in CRISPR-Cas12i1.

Nat Commun 2021 06 9;12(1):3476. Epub 2021 Jun 9.

The Key Laboratory of Innate Immune Biology of Fujian Province, Provincial University Key Laboratory of Cellular Stress Response and Metabolic Regulation, Biomedical Research Center of South China, Key Laboratory of OptoElectronic Science and Technology for Medicine of Ministry of Education, College of Life Sciences, Fujian Normal University, Fuzhou, China.

Cas12i is a newly identified member of the functionally diverse type V CRISPR-Cas effectors. Although Cas12i has the potential to serve as genome-editing tool, its structural and functional characteristics need to be investigated in more detail before effective application. Here we report the crystal structures of the Cas12i1 R-loop complexes before and after target DNA cleavage to elucidate the mechanisms underlying target DNA duplex unwinding, R-loop formation and cis cleavage. The structure of the R-loop complex after target DNA cleavage also provides information regarding trans cleavage. Besides, we report a crystal structure of the Cas12i1 binary complex interacting with a pseudo target oligonucleotide, which mimics target interrogation. Upon target DNA duplex binding, the Cas12i1 PAM-interacting cleft undergoes a remarkable open-to-closed adjustment. Notably, a zipper motif in the Helical-I domain facilitates unzipping of the target DNA duplex. Formation of the 19-bp crRNA-target DNA strand heteroduplex in the R-loop complexes triggers a conformational rearrangement and unleashes the DNase activity. This study provides valuable insights for developing Cas12i1 into a reliable genome-editing tool.
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http://dx.doi.org/10.1038/s41467-021-23876-5DOI Listing
June 2021

Mass cytometry and transcriptomic profiling reveal body-wide pathology induced by Loxl1 deficiency.

Cell Prolif 2021 Jun 9:e13077. Epub 2021 Jun 9.

Clinical Research Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

Objective: The loss of LOXL1 expression reportedly leads to the prolapse of pelvic organs or to exfoliation syndrome glaucoma. Increasing evidence suggests that LOXL1 deficiency is associated with the pathogenesis of several other diseases. However, the characterization of the systemic functions of LOXL1 is limited by the lack of relevant investigative technologies.

Materials And Methods: To determine the functions of LOXL1, a novel method for body-wide organ transcriptome profiling, combined with single-cell mass cytometry, was developed. A body-wide organ transcriptomic (BOT) map was created by RNA-Seq of tissues from 17 organs from both Loxl1 knockout (KO) and wild-type mice.

Results: The BOT results indicated the systemic upregulation of genes encoding proteins associated with the immune response and proliferation processes in multiple tissues of KO mice, and histological and immune staining confirmed the hyperplasia and infiltration of local immune cells in the tissues of KO mice. Furthermore, mass cytometry analysis of peripheral blood samples revealed systemic immune changes in KO mice. These findings were well correlated with results obtained from cancer databases. Patients with tumours had higher Loxl1 mutation frequencies, and patients with Loxl1-mutant tumours showed the upregulation of immune processes and cell proliferation and lower survival rates.

Conclusion: This study provides an effective strategy for the screening of gene functions in multiple organs and also illustrates the important biological roles of LOXL1 in the cells of multiple organs as well as in systemic immunity.
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http://dx.doi.org/10.1111/cpr.13077DOI Listing
June 2021

A new thermostable Cu(II) coordination polymer: photocatalytic activity and application values on diabetes.

Des Monomers Polym 2021 May 7;24(1):136-144. Epub 2021 May 7.

Department of Hepatobiliary Surgery, Zhuji People's Hospital of Zhejiang Province, Zhuji, Zhejiang, China.

A Cu(II) coordination polymer with the composition of [Cu(L)(4,4'-bipy)]·2 n(ClO) (, HL = 4-methyl-L-phenylalanine and 4,4'-bipy is 4,4'-bipyridine), was successfully obtained by the reaction of the mixed ligand of HL and 4,4'-bipy with Cu(ClO) · 6HO under solvothermal condition. The as-synthesized compound not only has high thermal stability until 275°C but also excellent photocatalytic activity for the methyl blue solution degradation under the irradiation of ultraviolet light. Furthermore, the compound's treatment activity on the diabetes was determined and its relevant mechanism was also studied. The cytotoxicity or hemolysis toxicity (HC50) of the synthesized compound was also evaluated in this research.
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http://dx.doi.org/10.1080/15685551.2021.1921341DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8118421PMC
May 2021

Toxicity remission of PAEs on multireceptors after molecular modification through a 3D-QSAR pharmacophore model coupled with a gray interconnect degree method.

Authors:
Xinyi Chen Yu Li

Turk J Chem 2021 28;45(2):307-322. Epub 2021 Apr 28.

MOE Key Laboratory of Resource and Environmental System Optimization, Ministry of Education,North China Electric Power University, Beijing China.

In the proposed model, the gray interconnect degree method was employed to process the acute toxicity values of phthalate acid esters (PAEs) to green algae, daphnia, mysid, and fish (predicted by EPI Suite software) and to obtain the comprehensive characterization value of the multireceptor toxicity effect (MTE) of PAEs. The 3D-QSAR pharmacophore model indicated that hydrophobic groups significantly affected the MTE of PAEs. Based on this, 16 PAEs derivative molecules with significantly decreased comprehensive characterization value (more than 10%) of the toxic effects of multireceptors were designed. Among them, 13 PAEs derivative molecules reduced the toxicity values (predicted by the EPI Suite software) of four receptor organisms to varying degrees. Finally, two derivative molecules from PAEs were screened and could exist stably in the environment. The derivative molecule's reduced toxicity to the receptor was obtained through molecular docking methods and simulated the PAEs' primary metabolic response pathways. The above research results break through the pharmacophore model's limitation of only being suitable for the single effect of pollutants. Its application provides a new theoretical verification basis for expanding the multieffect pharmacophore model.
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http://dx.doi.org/10.3906/kim-2008-38DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8164199PMC
April 2021

Nuclear translocation of the 4-pass transmembrane protein Tspan8.

Cell Res 2021 Jun 7. Epub 2021 Jun 7.

State Key Laboratory of Oncogenes and Related Genes, Department of Oncology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

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http://dx.doi.org/10.1038/s41422-021-00522-9DOI Listing
June 2021

A human antibody of potent efficacy against SARS-CoV-2 in rhesus macaques showed strong blocking activity to B.1.351.

MAbs 2021 Jan-Dec;13(1):1930636

Shanghai Jemincare Pharmaceuticals Co., Ltd., Shanghai, People's Republic of China.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which causes coronavirus disease-2019 (COVID-19), interacts with the host cell receptor angiotensin-converting enzyme 2 (hACE2) via its spike 1 protein during infection. After the virus sequence was published, we identified two potent antibodies against the SARS-CoV-2 receptor binding domain (RBD) from antibody libraries using a phage-to-yeast (PtY) display platform in only 10 days. Our lead antibody JMB2002, now in a Phase 1 clinical trial (ChiCTR2100042150), showed broad-spectrum blocking activity against hACE2 binding to the RBD of multiple SARS-CoV-2 variants, including B.1.351 that was reportedly much more resistant to neutralization by convalescent plasma, vaccine sera and some clinical-stage neutralizing antibodies. Furthermore, JMB2002 has demonstrated complete prophylactic and potent therapeutic efficacy in a rhesus macaque disease model. Prophylactic and therapeutic countermeasure intervention of SARS-CoV-2 using JMB2002 would likely slow down the transmission of currently emerged SARS-CoV-2 variants and result in more efficient control of the COVID-19 pandemic.
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http://dx.doi.org/10.1080/19420862.2021.1930636DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8189090PMC
June 2021

[Identification of a novel missense variant of the KAT6B gene in a child with Say-Barber-Biesecker-Young-Simpson syndrome].

Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2021 Jun;38(6):561-564

Department of Pediatrics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510120, China.

Objective: To explore the genetic basis for a child suspected for Say-Barber-Biesecker-Young-Simpson syndrome.

Methods: Genomic DNA was extracted from peripheral blood samples of the child and her parents. Whole exome sequencing was carried out for the proband. Suspected variants were validated by Sanger sequencing. The impact of the variants was predicted by bioinformatic analysis.

Results: The child was found to harbor a de novo missense variant c.2623C>T (p.Asp875Tyr) in exon 13 of the KAT6B gene. The variant was previously unreported, and was not recorded in the major allele frequency database and predicted to be pathogenic based on PolyPhen-2, MutationTaster and PROVEAN analysis. As predicted by UCSF chimera and CASTp software, the variant can severely impact the substrate-binding pocket of histone acetyltransferase, resulting in loss of its enzymatic activity. Based on standards and guidelines by the American College of Medical Genetics and Genomics, the variant was classified to be likely pathogenic (PS2+PM2+PP3).

Conclusion: The child's condition may be attributed to the de novo missense c.2623C>T (p.Asp875Tyr) variant of the KAT6B gene.
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http://dx.doi.org/10.3760/cma.j.cn511374-20200423-00299DOI Listing
June 2021

FUT8-AS1 Inhibits the Malignancy of Melanoma Through Promoting miR-145-5p Biogenesis and Suppressing NRAS/MAPK Signaling.

Front Oncol 2020 19;10:586085. Epub 2021 May 19.

Department of Intensive Care Unit, The 969th Hospital of PLA, Hohhot, China.

Melanoma is the major lethal skin malignancy. However, the critical molecular drivers governing melanoma progression and prognosis are still not clear. By analyzing The Cancer Genome Atlas (TCGA) data, we identified FUT8-AS1 as a prognosis-related long non-coding RNA (lncRNA) in melanoma. We further confirmed that FUT8-AS1 is downregulated in melanoma. Reduced expression of FUT8-AS1 is correlated with aggressive clinical factors and inferior overall survival. Using functional assays, our findings demonstrated that ectopic expression of FUT8-AS1 represses melanoma cell proliferation, migration, and invasion. FUT8-AS1 silencing promotes melanoma cell proliferation, migration, and invasion. Furthermore, functional assays demonstrated that FUT8-AS1 represses melanoma growth and metastasis. Mechanistically, FUT8-AS1 was found to bind NF90, repress the interaction between NF90 and primary miR-145 (pri-miR-145), relieve the repressive roles of NF90 on mature miR-145-5p biogenesis, and thus promote miR-145-5p biogenesis and upregulate mature miR-145-5p level. The expression of FUT8-AS1 is positively correlated with miR-145-5p in melanoma tissues. upregulating miR-145-5p, FUT8-AS1 reduces the expression of NRAS, a target of miR-145-5. FUT8-AS1 further represses MAPK signaling downregulating NRAS. Functional rescue assays demonstrated that inhibition of miR-145-5p reverses the tumor suppressive roles of FUT8-AS1 in melanoma. The oncogenic roles of FUT8-AS1 silencing are also blocked by MAPK signaling inhibitor MEK162. In conclusion, these findings demonstrate that FUT8-AS1 exerts tumor suppressive roles in melanoma regulating NF90/miR-145-5p/NRAS/MAPK signaling axis. Targeting FUT8-AS1 and its downstream molecular signaling axis represent promising therapeutic strategies for melanoma.
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http://dx.doi.org/10.3389/fonc.2020.586085DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8170315PMC
May 2021

Galvanic Vestibular Stimulation Improves Subnetwork Interactions in Parkinson's Disease.

J Healthc Eng 2021 13;2021:6632394. Epub 2021 May 13.

Pacific Parkinson's Research Centre, Vancouver, Canada.

Background: Activating vestibular afferents via galvanic vestibular stimulation (GVS) has been recently shown to have a number of complex motor effects in Parkinson's disease (PD), but the basis of these improvements is unclear. The evaluation of network-level connectivity changes may provide us with greater insights into the mechanisms of GVS efficacy.

Objective: To test the effects of different GVS stimuli on brain subnetwork interactions in both health control (HC) and PD groups using fMRI.

Methods: FMRI data were collected for all participants at baseline (resting state) and under noisy, 1 Hz sinusoidal, and 70-200 Hz multisine GVS. All stimuli were given below sensory threshold, blinding subjects to stimulation. The subnetworks of 15 healthy controls and 27 PD subjects (on medication) were identified in their native space, and their subnetwork interactions were estimated by nonnegative canonical correlation analysis. We then determined if the inferred subnetwork interaction changes were affected by disease and stimulus type and if the stimulus-dependent GVS effects were influenced by demographic features.

Results: At baseline, interactions with the visual-cerebellar network were significantly decreased in the PD group. Sinusoidal and multisine GVS improved (i.e., made values approaching those seen in HC) subnetwork interactions more effectively than noisy GVS stimuli overall. Worsening disease severity, apathy, depression, impaired cognitive function, and increasing age all limited the beneficial effects of GVS.

Conclusions: Vestibular stimulation has widespread system-level brain influences and can improve subnetwork interactions in PD in a stimulus-dependent manner, with the magnitude of such effects associating with demographics and disease status.
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http://dx.doi.org/10.1155/2021/6632394DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8137296PMC
May 2021

Mechanism underlying the regulation of lncRNA ACTA2-AS1 on CXCL2 by absorbing miRNA-532-5p as ceRNA in the development of ovarian cancer.

Int J Clin Exp Pathol 2021 15;14(5):596-607. Epub 2021 May 15.

Department of Gynecology and Obstetrics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital Shanghai, China.

Objective: To explore the mechanism underlying the regulation of long non-coding RNA (LncRNA) ACTA2-AS1 on CXCL2 as a ceRNA of miR-532-5p in the progression of ovarian cancer (OC).

Methods: A qRT-PCR assay was carried out for analyzing the expression changes of ACTA2-AS1, miR-532-5p, as well as CXCL2 in OC tissues and corresponding healthy paracancerous tissues HOSEpiC (human ovarian epithelial cells), and OC cells. OC cells were grouped and transfected, and the fluorescent in situ hybridization was adopted for evaluating ACTA2-AS1 in the cells. Additionally, a dual luciferase reporter (DLR) assay was carried out for verifying the correlation of ACTA2-AS1 with miR-532-5p and of miR-532-5p with CXCL2. Cells were transfected with si-ACTA2-AS1, miR-532-5p, or CXCL2 overexpression plasmids, and then the cell proliferation, invasion, and apoptosis were determined using MTT, Transwell, and flow cytometry assays, respectively.

Results: Compared with paracancerous tissues and HOSEpiC cells, OC tissues and cells showed increased ACTA2-AS1 and CXCL2 expression and decreased miR-532-5p expression (all P<0.05). ACTA2-AS1 acted as ceRNA in OC by negatively regulating miR-532-5p. Additionally, upregulating ACTA2-AS1 intensified the proliferation and invasion of cancer cells and suppressed their apoptosis (all P<0.05), and inhibition of it resulted in opposite results. In contrast, overexpressing miR-532-5p suppressed the proliferation, invasion, and clone formation of the cells and promoted their apoptosis (all P<0.05). The effect of ACTA2-AS1 on OC cells can be partially reversed by overexpressing miR-532-5p. Moreover, CXCL2, positively correlated with ACTA2-AS1 in expression (P<0.0001, r=0.7385), was the target of miR-532-5p, and its overexpression could partially offset the influence of miR-532-5p on OC cells.

Conclusion: LncRNA ACTA2-AS1 can act as a tumor promoter in OC by absorbing miR-532-5p as ceRNA and regulating CXCL2, and ACTA2-AS1 inhibitor is expected to play a role in targeted therapy of OC.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8167494PMC
May 2021

Exhausting circ_0136474 and Restoring miR-766-3p Attenuate Chondrocyte Oxidative Injury in IL-1β-Induced Osteoarthritis Progression Through Regulating DNMT3A.

Front Genet 2021 21;12:648709. Epub 2021 May 21.

Department of Orthopaedic Trauma and Microsurgery, Zhongnan Hospital of Wuhan University, Wuhan, China.

Circular RNA circ_0136474 is a new contributor of human osteoarthritis (OA) by suppressing chondrocyte proliferation. However, its role and mechanism in OA chondrocyte injury remain ill defined. Herein, we performed real-time quantitative PCR to detect RNA expression of circ_0136474, microRNA (miR)-766-3p, and DNA methyltransferase 3A (DNMT3A) and utilized Western blotting to measure protein expression of DNMT3A, matrix metalloproteinase-1 (MMP1), MMP13, collagen II, proliferating cell nuclear antigen (PCNA) and B cell lymphoma (Bcl)-2, and Bcl-2-associated X protein (Bax). Direct interaction between miR-766-3p and circ_0136474 or DNMT3A was confirmed by bioinformatics algorithms, dual-luciferase reporter assay, and RNA immunoprecipitation. Functional experiments including cell counting kit-8 assay, flow cytometry, and special assay kits were employed to measure oxidative injury in interleukin (IL)-1β-induced OA-like chondrocytes. First, IL-1β administration induced cell viability inhibition, collagen II suppression, and promotion of MMP1 and MMP13 in human chondrocyte CHON-001 cells. Expression of circ_0136474 and DNMT3A was upregulated, and miR-766-3p was downregulated in human OA cartilages and IL-1β-induced CHON-001 cells. Functionally, both blocking circ_0136474 and upregulating miR-766-3p could rescue cell viability and levels of PCNA, Bcl-2, reduced glutathione (GSH), and total superoxide dismutase (SOD), and attenuate apoptosis rate and levels of Bax, reactive oxygen species (ROS), and lipid peroxidation malondialdehyde (MDA). Mechanically, circ_0136474 served as miR-766-3p sponge to govern miR-766-3p-targeted DNMT3A expression. Accidently, restoring DNMT3A counteracted the miR-766-3p upregulation role, and silencing miR-766-3p weakened circ_0136474 knockdown effect in IL-1β-induced CHON-001 cells. In conclusion, exhausting circ_0136474 could mitigate OA chondrocyte oxidative injury through regulating miR-766-3p/DNMT3A axis.
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http://dx.doi.org/10.3389/fgene.2021.648709DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8177824PMC
May 2021

Water Splitting Induced by Visible Light at a Copper-Based Single-Molecule Junction.

Small 2021 Jun 4:e2008109. Epub 2021 Jun 4.

Department of Chemistry, School of Science, Tokyo Institute of Technology, 2-12-1 Ookayama, Meguro-ku, Tokyo, 152-8551, Japan.

Water splitting is an essential process for converting light energy into easily storable energy in the form of hydrogen. As environmentally preferable catalysts, Cu-based materials have attracted attention as water-splitting catalysts. To enhance the efficiency of water splitting, a reaction process should be developed. Single-molecule junctions (SMJs) are attractive structures for developing these reactions because the molecule electronic state is significantly modulated, and characteristic electromagnetic effects can be expected. Here, water splitting is induced at Cu-based SMJ and the produced hydrogen is characterized at a single-molecule scale by employing electron transport measurements. After visible light irradiation, the conductance states originate from Cu/hydrogen molecule/Cu junctions, while before irradiation, only Cu/water molecule/Cu junctions were observed. The vibration spectra obtained from inelastic electron tunneling spectroscopy combined with the first-principles calculations reveal that the water molecule trapped between the Cu electrodes is decomposed and that hydrogen is produced. Time-dependent and wavelength-dependent measurements show that localized-surface plasmon decomposes the water molecule in the vicinity of the junction. These findings indicate the potential ability of Cu-based materials for photocatalysis.
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http://dx.doi.org/10.1002/smll.202008109DOI Listing
June 2021

Two conifer GUX clades are responsible for distinct glucuronic acid patterns on xylan.

New Phytol 2021 Jun 4. Epub 2021 Jun 4.

Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QW, United Kingdom.

Wood of coniferous trees (softwood), is a globally significant carbon sink and an important source of biomass. Despite that, little is known about the genetic basis of softwood cell wall biosynthesis. Branching of xylan, one of the main hemicelluloses in softwood secondary cell walls, with glucuronic acid (GlcA) is critical for biomass recalcitrance. Here, we investigate the decoration patterns of xylan by conifer GlucUronic acid substitution of Xylan (GUX) enzymes. Through molecular phylogenetics we identify two distinct conifer GUX clades. Using transcriptional profiling we show that the genes are preferentially expressed in secondary cell wall forming tissues. With in vitro and in planta assays we demonstrate that conifer GUX enzymes from both clades are active glucuronyltransferases. Conifer GUX enzymes from each clade have different specific activities. While members of clade one add evenly spaced GlcA branches, the members of clade two are also capable of glucuronidating two consecutive xyloses. Importantly, these types of xylan patterning are present in softwood. Since xylan patterning might modulate xylan-cellulose and xylan-lignin interactions, our results further the understanding of softwood cell wall biosynthesis and provide breeding or genetic engineering targets that can be used to modify softwood properties.
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http://dx.doi.org/10.1111/nph.17531DOI Listing
June 2021

"Shared Decision Making Assistant": A Smartphone Application to Meet the Decision-Making Needs of Patients With Primary Liver Cancer.

Comput Inform Nurs 2021 Jun 2. Epub 2021 Jun 2.

Author Affiliations: Department of Nursing (Drs Wang, Ye, Yunyun Li, and L. Li), Department of No. 3 Hepatobiliary Surgery (Dr Pan), Department of No. 5 Hepatobiliary Surgery (Dr Yang), and Department of Organ Transplantation (Dr Yu Li), Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, PR China.

The development of medical technology provides medical specialists with a variety of choices for their primary liver cancer patients, including partial liver resection, transcatheter arterial chemoembolization, liver transplantation, and so on. However, in this context, because patients with primary liver cancer frequently do not receive adequate information to help make complicated medical decisions, those patients, who are usually otherwise ignorant about their disease, are facing multiple difficult choices. The problem might be alleviated with a process called "shared decision making." Accordingly, researchers developed a smartphone application named "Shared Decision Making Assistant" for primary liver cancer patients in China, and in this article, we report the process of its development. First, individual interviews were conducted to identify the specific needs and status of primary liver cancer patients participating in shared decision making. Next, expert group discussions were held among primary liver cancer medical experts, nurses, and software engineers, using a decision-making process called the Delphi method, which was used to arrive at a group opinion or decision by surveying a panel of experts, to draft the framework and decide on the contents of the mobile health-based decision aids program. Feedbacks and suggestions were collected to optimize the workflow of "Shared Decision Making Assistant." The resulting application consisted of seven modules: personal information, primary liver cancer treatment knowledge center, decision aids path, continuing care, interactive platform, health education, and backstage management.
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http://dx.doi.org/10.1097/CIN.0000000000000775DOI Listing
June 2021

Psychological Impact During the First Outbreak of COVID-19 on Frontline Health Care Workers in Shanghai.

Front Public Health 2021 17;9:646780. Epub 2021 May 17.

Department of Pulmonary and Critical Care Medicine, Shanghai Fifth People's Hospital, Fudan University, Shanghai, China.

The COVID-19 pandemic is a significant health threat. Health care worker (HCWs) are at a significant risk of infection which may cause high levels of psychological distress. The aim of this study was to investigate the psychological impact of the COVID-19 on HCWs and factors which were associated with these stresses during the first outbreak in Shanghai. Between February 9 and 21, 2020, a total of 3,114 frontline HCWs from 26 hospitals in Shanghai completed an online survey. The questionnaire included questions on their sociodemographic characteristics, 15 stress-related questions, and General Health Questionnaire-12 (GHQ-12). Exploratory factor analysis was applied to the 15 stress-related questions which produced four distinct factors for evaluation. Multiple linear regression models were performed to explore the association of personal characteristics with each score of the four factors. Binary logistic analysis was used to explain the association of personal characteristics and these four factors with the GHQ-12. There were 2,691 valid surveys received. The prevalence of emotional distress (defined as GHQ-12 ≥ 12) was noted in 47.7% (95%CI:45.7-49.6%) HCWs. Females (OR = 1.43, 95%CI:1.09-1.86) were more likely to have a psychological distress than males. However, HCWs who work in secondary hospitals (OR = 0.71, 95% CI:0.58-0.87) or had a no contact history (OR = 0.45, 95%CI: 0.35-0.58) were less likely to suffer psychological distress. HCWs who were nurses, married, and had a known contact history were highly likely to have anxiety. HCWs working at tertiary hospitals felt an elevated anxiety regarding the infection, a lack of knowledge, and less protected compared to those who worked at secondary hospitals. Our study shows that the frontline HCWs had a significant psychosocial distress during the COVID-19 outbreak in Shanghai. HCWs felt a lack of knowledge and had feelings of being not protected. It is necessary for hospitals and governments to provide additional trainings and psychological counseling to support the first-line HCWs.
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http://dx.doi.org/10.3389/fpubh.2021.646780DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8165161PMC
June 2021

Imaging features of mycotic aortic aneurysms.

Quant Imaging Med Surg 2021 Jun;11(6):2861-2878

Department of Cardiovascular Surgery, Beijing Aortic Disease Centre, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart Lung and Blood Vessel Diseases, Beijing Engineering Research Centre for Vascular Prostheses, Beijing, China.

Infectious aortitis (IA) is a rare and life-threatening cardiovascular disease. Early diagnosis and timely intervention are crucial for reducing mortality associated with mycotic aortic aneurysms (MAAs); however, early diagnosis is challenging due to the nonspecific symptoms. Some cases are diagnosed at an advanced stage or after developing complications, such as rupture or aortic fistula. Current state-of-the-art imaging modalities-including computed tomography (CT), magnetic resonance imaging (MRI), and 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT-can detect infected aneurysms in clinically suspicious cases. MAA features on imaging include lobulated pseudoaneurysm, indistinct irregular arterial wall, perianeurysmal gas, perianeurysmal edema, perianeurysmal soft tissue mass, aneurysmal thrombosis, and high metabolic activity with increased uptake of FDG. Enlarged lymph nodes are often found adjacent to the aneurysm, while iliopsoas abscess (IPA), spondylitis, and aortic fistulas are commonly associated complications. After surgery or endovascular repair, radiological features-including ectopic gas, peri-graft fluid, thickening of adjacent bowel, pseudoaneurysm formed at the graft anastomosis, and increased uptake of FDG-may indicate an infection of aortic graft. This article provides an overview of the clinical and imaging features of MAAs. Thus, familiarity with the imaging appearances of MAAs may assist radiologists in the diagnosis and facilitation of timely treatment.
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http://dx.doi.org/10.21037/qims-20-941DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8107294PMC
June 2021

Fibrinogen-mimicking, multiarm nanovesicles for human thrombus-specific delivery of tissue plasminogen activator and targeted thrombolytic therapy.

Sci Adv 2021 Jun 2;7(23). Epub 2021 Jun 2.

Department of Chemical Engineering, Imperial College London, South Kensington Campus, London, UK.

Clinical use of tissue plasminogen activator (tPA) in thrombolytic therapy is limited by its short circulation time and hemorrhagic side effects. Inspired by fibrinogen binding to activated platelets, we report a fibrinogen-mimicking, multiarm nanovesicle for thrombus-specific tPA delivery and targeted thrombolysis. This biomimetic system is based on the lipid nanovesicle coated with polyethylene glycol (PEG) terminally conjugated with a cyclic RGD (cRGD) peptide. Our experiments with human blood demonstrated its highly selective binding to activated platelets and efficient tPA release at a thrombus site under both static and physiological flow conditions. Its clot dissolution time in a microfluidic system was comparable to that of free tPA. Furthermore, we report a purpose-built computational model capable of simulating targeted thrombolysis of the tPA-loaded nanovesicle and with a potential in predicting the dynamics of thrombolysis in physiologically realistic scenarios. This combined experimental and computational work presents a promising platform for development of thrombolytic nanomedicines.
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http://dx.doi.org/10.1126/sciadv.abf9033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8172176PMC
June 2021

Comparison of Upfront Transplantation and Pretransplant Cytoreductive Therapy for Advanced Myelodysplastic Syndrome.

Clin Lymphoma Myeloma Leuk 2021 Apr 28. Epub 2021 Apr 28.

School of Medicine, Nankai University, Tianjin, China; Department of Hematology, Chinese PLA General Hospital, Beijing, China; Department of Hematology and Oncology, International Cancer Center, Shenzhen Key Laboratory of Precision Medicine for Hematological Malignancies, Shenzhen University General Hospital, Shenzhen University Clinical Medical Academy, Shenzhen University Health Science Center, Shenzhen, China. Electronic address:

Background: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only curative therapy for advanced myelodysplastic syndrome (MDS). However, the value of pretransplant cytoreduction remains debatable.

Patients And Methods: We retrospectively compared the outcomes of upfront transplantation and pretransplant cytoreduction. Of 69 patients, 39 received upfront allo-HSCT and 30 received pretransplant cytoreduction, including chemotherapy (n = 16), hypomethylating agents (HMAs, n = 6), and HMAs with chemotherapy (n = 8).

Results: The upfront group achieved similar overall survival (OS) and a trend of better progression-free survival (PFS) from diagnosis compared with the cytoreduction group (3-year PFS, 64.0% vs. 44.4%, P = .076). Posttransplant outcomes were comparable between the two groups in terms of OS, relapse-free survival (RFS), cumulative incidence of relapse (CIR), and non-relapse mortality (NRM). In patients with ≥2 mutations, the upfront group achieved better OS and PFS (3-year OS, 100.0% vs. 68.6%, P = .044; 3-year PFS: 92.3% vs. 43.9%, P = .016) than the cytoreduction group. Patients achieving remission in the cytoreduction group had outcomes similar to the upfront group, but those without remission before transplantation had a significantly worse posttransplant OS (3-year OS, 46.7% vs. 75.7%, P = .038). Patients with pretransplant HMAs had better PFS than those with chemotherapy or HMAs plus chemotherapy (P < 0.05).

Conclusion: Compared with pretransplant cytoreduction, upfront allo-HSCT might provide more benefit to some patients with advanced MDS if there are suitable donors. HMAs would be a good alternative during the donor search.
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http://dx.doi.org/10.1016/j.clml.2021.04.015DOI Listing
April 2021

Mitigating the Adverse Effects of Polychlorinated Biphenyl Derivatives on Estrogenic Activity via Molecular Modification Techniques.

Int J Environ Res Public Health 2021 05 8;18(9). Epub 2021 May 8.

MOE Key Laboratory of Resources Environmental Systems Optimization, College of Environmental Science and Engineering, North China Electric Power University, Beijing 102206, China.

The aim of this paper is to explore the mechanism of the change in oestrogenic activity of PCBs molecules before and after modification by designing new PCBs derivatives in combination with molecular docking techniques through the constructed model of oestrogenic activity of PCBs molecules. We found that the weakened hydrophobic interaction between the hydrophobic amino acid residues and hydrophobic substituents at the binding site of PCB derivatives and human oestrogen receptor alpha (hERα) was the main reason for the weakened binding force and reduced anti-oestrogenic activity. It was consistent with the information that the hydrophobic field displayed by the 3D contour maps in the constructed oestrogen activity CoMSIA model was one of the main influencing force fields. The hydrophobic interaction between PCB derivatives and oestrogen-active receptors was negatively correlated with the average distance between hydrophobic substituents and hydrophobic amino acid residues at the hERα-binding site, and positively correlated with the number of hydrophobic amino acid residues. In other words, the smaller the average distance between the hydrophobic amino acid residues at the binding sites between the two and the more the number of them, and the stronger the oestrogen activity expression degree of PCBS derivative molecules. Therefore, hydrophobic interactions between PCB derivatives and the oestrogen receptor can be reduced by altering the microenvironmental conditions in humans. This reduces the ability of PCB derivatives to bind to the oestrogen receptor and can effectively modulate the risk of residual PCB derivatives to produce oestrogenic activity in humans.
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http://dx.doi.org/10.3390/ijerph18094999DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8125871PMC
May 2021

Outcomes and Loop Pattern Analysis of a Road-Map Technique for ERCP with Side-Viewing Duodenoscope in Patients with Billroth II Gastrectomy (with Video).

J Pers Med 2021 May 12;11(5). Epub 2021 May 12.

Department of Gastroenterology, Ajou University School of Medicine, 164 Worldcup-ro, Yeongtong-gu, Suwon 16499, Korea.

Endoscopic retrograde cholangiopancreatography (ERCP) in patients who have undergone a Billroth II gastrectomy is a major challenge. This study aimed to evaluate the outcomes of the road-map technique for duodenal intubation using a side-viewing duodenoscope for ERCP in Billroth II gastrectomy patients with naïve papilla, and to analyze the formation and release patterns of common bowel loops that occur when the duodenoscope navigates the afferent limb. The duodenoscopy approach success rate was 85.8% (97/113). In successful duodenoscopy approach patients, there were five bowel looping patterns that occurred when the preceding catheter-connected duodenoscope was advanced into the duodenum: (1) reverse ɣ-loop (29.9%), (2) fixed reverse ɣ-loop (5.2%), (3) simple U-loop (22.7%), (4) N-loop (28.9%), and (5) reverse alpha loop (13.4%). The duodenoscopy cannulation and duodenoscopy therapeutic success rates were 81.4% (92/113) and 80.5% (91/113), respectively, while the overall cannulation and therapeutic success rates were 92.0% (104/113) and 87.6% (99/113), respectively. Bowel perforation occurred in three patients (2.7%). The road-map technique may benefit duodenoscope-based ERCP in Billroth II gastrectomy patients by minimizing the tangential axis alignment between the duodenoscopic tip and driving of the afferent limb, and by predicting and counteracting bowel loops that occur when the duodenoscope navigates the afferent limb.
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http://dx.doi.org/10.3390/jpm11050404DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8150314PMC
May 2021

Pillow Support Model with Partitioned Matching Based on Body Pressure Distribution Matrix.

Healthcare (Basel) 2021 May 12;9(5). Epub 2021 May 12.

College of Design and Architecture, Zhejiang University of Technology, Hangzhou 310023, China.

(1) Objective: Sleep problems have become one of the current serious public health issues. The purpose of this research was to construct an ideal pressure distribution model for head and neck support through research on the partitioned support surface of a pillow in order to guide the development of ergonomic pillows. (2) Methods: Seven typical memory foam pillows were selected as samples, and six subjects were recruited to carry out a body pressure distribution experiment. The average value of the first 10% of the samples in the comfort evaluation was calculated to obtain the relative ideal body pressure distribution matrix. Fuzzy clustering was performed on the ideal matrix to obtain the support surface partition. The ideal body pressure index of each partition was calculated, and a hierarchical analysis of each partition was then performed to determine the pressure sensitivity weight of each partition. Using these approaches, the key ergonomic node coordinates of the partitions of four different groups of people were extracted. The ergonomic node coordinates and the physical characteristics of the material were used to design a pillow prototype. Five subjects were recruited for each of the four groups to repeat the body pressure distribution experiment to evaluate the pillow prototype. (3) Results: An ideal support model with seven partitions, including three partitions in the supine position and four partitions in the lateral position, was constructed. The ideal body pressure distribution matrix and ideal body pressure indicators and pressure sensitivity weights for each partition were provided. The pillow that was designed and manufactured based on this model reproduced the ideal pressure distribution matrix evaluated by various groups of people. (4) Conclusion: The seven-partition ideal support model can effectively describe the head and neck support requirements of supine and lateral positions, which can provide strong support for the development of related products.
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http://dx.doi.org/10.3390/healthcare9050571DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8151739PMC
May 2021

Electromagnetically Induced Transparency-Like Effect by Dark-Dark Mode Coupling.

Nanomaterials (Basel) 2021 May 20;11(5). Epub 2021 May 20.

Department of Physics, Dalian University of Technology, Ganjingzi District, Dalian 116024, China.

Electromagnetically induced transparency-like (EIT-like) effect is a promising research area for applications of slow light, sensing and metamaterials. The EIT-like effect is generally formed by the destructive interference of bright-dark mode coupling and bright-bright mode coupling. There are seldom reports about EIT-like effect realized by the coupling of two dark modes. In this paper, we numerically and theoretically demonstrated that the EIT-like effect is achieved through dark-dark mode coupling of two waveguide resonances in a compound nanosystem with metal grating and multilayer structure. If we introduce |1⟩, |2⟩ and |3⟩ to represent the surface plasmon polaritons (SPPs) resonance, waveguide resonance in layer 2, and waveguide resonance in layer 4, the destructive interference occurs between two pathways of |0⟩→|1⟩→|2⟩ and |0⟩→|1⟩→|2⟩→|3⟩→|2⟩, where |0⟩ is the ground state without excitation. Our work will stimulate more studies on EIT-like effect with dark-dark mode coupling in other systems.
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http://dx.doi.org/10.3390/nano11051350DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8161169PMC
May 2021

Ultra-Highly Sensitive Hydrogen Chloride Detection Based on Quartz-Enhanced Photothermal Spectroscopy.

Sensors (Basel) 2021 May 20;21(10). Epub 2021 May 20.

National Key Laboratory of Science and Technology on Tunable Laser, Harbin Institute of Technology, Harbin 150001, China.

Combining the merits of non-contact measurement and high sensitivity, the quartz-enhanced photothermal spectroscopy (QEPTS) technique is suitable for measuring acid gases such as hydrogen chloride (HCl). In this invited paper, we report, for the first time, on an ultra-highly sensitive HCl sensor based on the QEPTS technique. A continuous wave, distributed feedback (CW-DFB) fiber-coupled diode laser with emission wavelength of 1.74 µm was used as the excitation source. A certified mixture of 500 ppm HCl:N was adapted as the analyte. Wavelength modulation spectroscopy was used to simplify the data processing. The wavelength modulation depth was optimized. The relationships between the second harmonic (2) amplitude of HCl-QEPTS signal and the laser power as well as HCl concentration were investigated. An Allan variance analysis was performed to prove that this sensor had good stability and high sensitivity. The proposed HCl-QEPTS sensor can achieve a minimum detection limit (MDL) of ~17 parts per billion (ppb) with an integration time of 130 s. Further improvement of such an HCl-QEPTS sensor performance was proposed.
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http://dx.doi.org/10.3390/s21103563DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8160860PMC
May 2021